An interventional study of PDR001 in adult patients with nasopharyngeal carcinoma (NPC) who have progressed on standard treatment

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2015-000454-38-FR
• Date of registration: 19/01/2016
• Prospective Registration: No
• Primary sponsor: Novartis Pharma Services AG
• Public title: An interventional study of PDR001 in adult patients with nasopharyngeal carcinoma (NPC) who have progressed on standard treatment
• Scientific title: A phase II, open-label, randomized controlled study of PDR001 in patients with moderately differentiated/undifferentiated locally advanced recurrent or metastatic nasopharyngeal carcinoma who progressed on standard treatment
• Date of first enrolment: 13/10/2015
• Target sample size: 109
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000454-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Other specify the comparator: Investigator's choice of chemotherapy; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, China, France, Hong Kong, Singapore, Taiwan, Thailand, United States

Contacts

• Name: Information&CommunicationMédicales
• Affiliation: Novartis Pharma S.A.S

• Name: Information&CommunicationMédicales
• Affiliation: Novartis Pharma S.A.S

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically documented non-keratinizing locally advanced recurrent or metastatic NPC.
2. Must be resistant to platinum-based chemotherapy (defined as progression on or after platinum-based chemotherapy given in the recurrent/metastatic setting).
3. May have received at least 1 prior therapy for recurrent or metastatic disease, up to 2 prior systemic therapies.
4. An archival tumor specimen or newly obtained tumor sample may be submitted at screening/baseline (a fresh tumor sample is preferred), unless agreed differently between Novartis and the Investigator.
5. At least 1 measurable lesion (as per RECIST v1.1) progressing or new since last anti-tumor therapy.
6. Prior treated brain or meningeal metastases must be without MRI evidence of progression for at least 8 weeks and off systemic steroids for at least 2 weeks prior to screening/baseline.
7. Patient must be willing to undergo testing for human immunodeficiency virus (HIV) if not tested within the past 6 months. If HIV+ positive, patient will be eligible if: his/ her CD4+ count = 300/µL; his/her viral load is undetectable; he/she is currently receiving highly active antiretroviral therapy (HAART).

Other protocol-defined inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 74

Exclusion criteria:
1. History of severe hypersensitivity reactions to other mAbs
2. Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved asthma/atopy that is treated with broncho-dilators.
3. Active HBV or HCV infections requiring therapy.
4. Prior PD-1- or PD-L1-directed therapy or any therapeutic cancer vaccine.
5. Patients receiving systemic treatment with any immunosuppressive medication.
6. Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within 4 weeks of initiation of study treatment.

Other protocol-defined exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderately differentiated/undifferentiated locally advanced recurrent or metastatic nasopharyngeal carcinoma

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: PDR001
Pharmaceutical Form: Lyophilisate for solution for infusion
Current Sponsor code: PDR001
Other descriptive name: PDR001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: PFS will be assessed after 70 events (progressive diseases or death due to any cause) are observed from the study

Primary end point(s): Progression free survival (PFS) as per RECIST v1.1 using central assessment

Secondary Objective: 1- To evaluate the anti-tumor activity of PDR001 versus
investigator ‘choice of chemotherapy in patients with moderately
differentiated/undifferentiated locally advanced recurrent or
metastatic NPC who progressed on or after first-line therapy
2- To characterize the safety and tolerability of PDR001
3- To characterize the pharmacokinetic profile of PDR001 (patients in PDR001 arm)
4- To assess emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001(patients in
PDR001 arm)
5- To assess the pharmacodynamic effect of PDR001 in peripheral blood (patients in PDR001 arm)

Main Objective: To assess the efficacy of PDR001 versus investigator’s choice
of chemotherapy in patients with moderately differentiated / undifferentiated locally advanced recurrent or metastatic NPC who progressed on or after first-line therapy

Secondary Outcome(s)

Secondary end point(s): 1- Overall survival (OS), overall response rate (ORR), duration of
response (DOR), time to progression (TTP) and immune related
progression free survival (irPFS) as per irRC using central
assessment
2- Safety: Incidence and severity of adverse events (AEs),immunorelated AEs (irAEs) and serious adverse events (SAEs), including changes in laboratory parameters, vital signs and electrocardiograms (ECGs)
3- Serum PK parameters (e.g. AUC, Cmax, Tmax, half-life); Serum concentration vs. time profiles
4- Presence and/or concentration of anti-PDR001 antibodies
5- Assess peripheral, soluble ligands and cytokine levels (including but not limited to IFN-?, TNF-a, IL-6)

Timepoint(s) of evaluation of this end point: 1- During treatment: 8 weeks after Cycle 1 Day 1, and then every 8 weeks until week 40. Then every 12 until progression or patient withdrawal
Follow up for progression: every 8 weeks until week 40, then every 12 weeks until progression or lost to follow-up
2- Assessed continously throughout study for all patients. ECGs during screening on Cycle 1 and 3 on Day 1 and at end of treatment
3- Cycle 1 and Cycle 3 on Day 1, 2, 8 and 15. Cycle 2 on Day 1, 8 and 15. Cycle 4, 5 and 6 on Day 1 and end of treatment
4- Cycle 1 to Cycle 6 on Day 1 and end of treatement
5- At Cycle 1 and Cycle 2 on Day 1, 8 and 15 (pre-dose) and end of treatment

Secondary ID(s)

CPDR001X2201

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 02/12/2015
Contact: